The collateral circulation is the only source of blood supply to the myocardium after an acute coronary occlusion. During recovery, it constitutes nature's own repair process by developing new vascular growth. Coronary occlusion often leads to heart failure with a concomitant increase in coronary venous pressure which, in turn, can have a further deleterious effect on coronary and collateral perfusion, hence, augments heart failure. The proposed studies represent a continuation of our investigations into the mechanism(s) underlying coronary collateral growth. Our recent confirmation that intramural collaterals constitute the major component of the collateral circulation in the dog, as it does in humans, warrants studies concerned with influences affecting their ability to provide blood to the collateral dependent myocardium. The methods for this quantitation are accurate and lend themselves to repeated measurements. Recent findings from this laboratory also point to the potential importance of the coronary venous system in influencing coronary and collateral perfusion and is the subject of investigations for this application. The specific aims of this proposal are: 1) To investigate whether a chronic increase in blood flow (velocity) provides a stimulus for coronary and/or collateral growth, 2) to identify, characterize, and quantitate the effects of myocardial forces on epicardial and intramural collateral flow in hearts with native and mature collaterals, 3) to study the effects of changes in coronary venous pressure on perfusion of the collateral dependent myocardium. The research will be performed in conscious dogs and an isolated heart system that allows the intrinsic influences of the heart on coronary flow to be studied independent of peripheral influences.